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Altered metabolism distinguishes high-risk from stable carotid atherosclerotic plaques

Author:
  • Lukas Tomas
  • Andreas Edsfeldt
  • Inês G Mollet
  • Ljubica Perisic Matic
  • Cornelia Prehn
  • Jerzy Adamski
  • Gabrielle Paulsson-Berne
  • Ulf Hedin
  • Jan Nilsson
  • Eva Bengtsson
  • Isabel Gonçalves
  • Harry Björkbacka
Publishing year: 2018-06-21
Language: English
Pages: 2301-2310
Publication/Series: European Heart Journal
Volume: 39
Issue: 24
Document type: Journal article
Publisher: Oxford University Press

Abstract english

Aims: Identification and treatment of the rupture prone atherosclerotic plaque remains a challenge for reducing the burden of cardiovascular disease. The interconnection of metabolic and inflammatory processes in rupture prone plaques is poorly understood. Herein, we investigate associations between metabolite profiles, inflammatory mediators and vulnerability in carotid atherosclerotic plaques.

Methods and results: We collected 159 carotid plaques from patients undergoing endarterectomy and measured 165 different metabolites in a targeted metabolomics approach. We identified a metabolite profile in carotid plaques that associated with histologically evaluated vulnerability and inflammatory mediators, as well as presence of symptoms in patients. The distinct metabolite profiles identified in high-risk and stable plaques were in line with different transcription levels of metabolic enzymes in the two groups, suggesting an altered metabolism in high-risk plaques. The altered metabolic signature in high-risk plaques was consistent with a change to increased glycolysis, elevated amino acid utilization and decreased fatty acid oxidation, similar to what is found in activated leucocytes and cancer cells.

Conclusion: These results highlight a possible key role of cellular metabolism to support inflammation and a high-risk phenotype of atherosclerotic plaques. Targeting the metabolism of atherosclerotic plaques with novel metabolic radiotracers or inhibitors might therefore be valid future approaches to identify and treat the high-risk atherosclerotic plaque.

Keywords

  • Cardiac and Cardiovascular Systems

Other

Published
  • Cardiovascular Research - Cellular Metabolism and Inflammation
  • Cardiovascular Research - Immunity and Athersosclerosis
  • Cardiovascular Research - Translational Studies
  • Diabetes - Islet Cell Exocytosis
  • Cardiovascular Research - Matrix and Inflammation in Atherosclerosis
  • ISSN: 1522-9645

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